Although not limited thereto, the invention applies to the treatment of “Sudden death” or out-of-hospital cardiac arrest which still represents a major public health issue. Its annual incidence reaches approximately 50,000 to 60,000 cases in France. A minor part of those patients can be resuscitated and further survive. They often exhibit severe neurological sequels and other dysfunctions resulting from the cardiac arrest. In addition to the dramatic consequences for these patients, this applies a high socioeconomic cost when the patients should be maintained in critical care unit for a long term.
Institution of mild “therapeutic” hypothermia (32-34° C.) during 24 to 36 hours after resuscitation is known to improve survival and neurological recovery in comatose survivors of cardiac arrest (“Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia”, Bernard•S A, Gray T W, Buist M D, Jones B M, Silvester W, Gutteridge G, Smith K, N Engl J Med, 2002; 346:557-563; “Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest”, The Hypothermia After Cardiac Arrest Study Group, N Engl J Med. 2002; 346:549-556).
However, experimental studies in dogs (“Mild hypothermia during prolonged cardiopulmonary cerebral resuscitation increases conscious survival in dogs”, Nozari A, Safar P, Stezoski S W, Wu X, Henchir J, Radovsky A, Hanson K, Klein E, Kochanek P M, Tisherman S A, Crit Care Med, 2004; 32:2110-2116; “Critical time window for intra-arrest cooling with cold saline flush in a dog model of cardiopulmonary resuscitation”, Nozari A, Safar P, Stezoski S W, Wu X, Kostelnik S, Radovsky A, Tisherman S, Kochanek P M, Circulation 2006; 113:2690-2696), pigs (“A comparison between head cooling begun during cardiopulmonary resuscitation and surface cooling after resuscitation in a pig model of cardiac arrest”, Guan J, Barbut D, Wang H, Li Y, Tsai M S, Sun S, Inderbitzen B, Weil M H, Tang W, Crit Care Med, 2008; 36:S428-433; “Rapid head cooling initiated coincident with cardiopulmonary resuscitation improves success of defibrillation and post-resuscitation myocardial function in a porcine model of prolonged cardiac arrest”, Tsai M S, Barbut D, Tang W, Wang H, Guan J, Wang T, Sun S, Inderbitzen B, Weil M H, J Am Coll Cardiol, 2008; 51:1988-1990) and rodents (“Intra-arrest cooling with delayed reperfusion yields higher survival than earlier normothermic resuscitation in a mouse model of cardiac arrest”, Zhao D, Abella B S, Beiser D G, Alvarado J P, Wang H, Hamann K J, Hoek T L, Becker L B, Resuscitation, 2008; 77:242-249; “Intra-arrest cooling improves outcomes in a murine cardiac arrest model”, Abella B S, Zhao D, Alvarado J, Hamann K, Vanden Hoek T L, Becker L B, Circulation, 2004; 109:2786-2791) demonstrated that the neuroprotection afforded by hypothermia was related to the rapidity in body temperature decrease after resuscitation. When achieved rapidly, hypothermia could also be beneficial for other organs since it can be, for example, also potently cardioprotective during myocardial ischemia (“Hypothermia during reperfusion limits no-reflow injury in a rabbit model of acute myocardial infarction”, Hale S L, Dae M W, Kloner R A, Cardiovasc Res, 2003; 59:715-722; “Second window of protection against infarction in conscious rabbits: real or artifactual”, Miki T, Swafford A N, Cohen M V, Downey J M, J Mol Cell Cardiol, 1999; 31:809-816; “Rapid cooling preserves the ischaemic myocardium against mitochondrial damage and left ventricular dysfunction”, Tissier R, Couvreur N, Ghaleh B, Bruneval P, Lidouren F, Morin D, Zini R, Bize A, Chenoune M, Belair M F, Mandet C, Douheret M, Dubois-Rande J L, Parker J C, Cohen M V, Downey J M, bordeaux, A Cardiovasc Res, 2009; 83:345-353; “The small chill: mild hypothermia for cardioprotection?”, Tissier R, Chenoune M, Ghaleh B, Cohen M V, Downey J M, Berdeaux A, Cardiovasc Res, 2010; 88:406-414).
Accordingly, many strategies were proposed to afford such a rapid hypothermia, including intravenous infusion of cold fluid (“Cold saline infusion and ice packs alone are effective in inducing and maintaining therapeutic hypothermia after cardiac arrest”, Larsson I M, Wallin E, Rubertsson S, Resuscitatio, 2010; 81:15-19), endovascular or intranasal cooling (“Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction”, Dixon S R, Whitbourn R J, Dae M W, Grube E, Sherman W, Schaer G L, Jenkins J S, Bairn D S, Gibbons R J, Kuntz R E, Popma J J, Nguyen T T, O'Neill W W, J Am Coll Cardiol, 2002; 40:1928-1934; “Survival and neurological outcomes after nasopharyngeal cooling or peripheral vein cold saline infusion initiated during cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest”, Yu T, Barbut D, Ristagno G, Cho J H, Sun S, Li Y, Weil M H, Tang W, Crit Care Med, 2010; 38:916-921; “Feasibility of intra-arrest hypothermia induction: A novel nasopharyngeal approach achieves preferential brain cooling”, Boller M, Lampe J W, Katz J M, Barbut D, Becker L B, Resuscitation, 2010; 81:1025-1030).
Besides, total liquid ventilation that alternatively instillates and removes a tidal volume of perfluorocarbon from the lungs has already been used to decrease rapidly the left atrial temperature in rabbits. This was associated with a very potent protection against myocardial infarction and subsequent contractile dysfunction in animal models of coronary artery occlusion (“Rapid cooling of the heart with total liquid ventilation prevents transmural myocardial infarction following prolonged ischemia in rabbits”, Chenoune M, Lidouren F, Ghaleh B, Couvreur N, Dubois-Rande J-L, Berdeaux A, Tissier R, Resuscitation, 2010; 81:359-362; “Total liquid ventilation provides ultra-fast cardioprotective cooling”, Tissier R, Hamanaka K, Kuno A, Parker J C, Cohen M V, Downey J M, J Am Coll Cardiol, 2007; 49:601-605). In a swine model of ventricular fibrillation, liquid ventilation also induced a rapid convective cooling that further improves the chances for subsequent resumption of spontaneous circulation (“Intra-arrest hypothermia: both cold liquid ventilation with perfluorocarbons and cold intravenous saline rapidly achieve hypothermia, but only cold liquid ventilation improves resumption of spontaneous circulation”, Riter H G, Brooks L A, Pretorius A M, Ackermann L W, Kerber R E, Resuscitation, 2009; 80:561-566; “Liquid ventilation with perfluorocarbons facilitates resumption of spontaneous circulation in a swine cardiac arrest model”, Staffey K S, Dendi R, Brooks L A, Pretorius A M, Ackermann L W, Zamba K D, Dickson E, Kerber R E, Resuscitation, 2008; 78:77-84).
However, the effect of hypothermic total liquid ventilation (TLV) instituted after cardiac arrest has never been investigated for post-cardiac arrest dysfunctions.
The invention aims to improve the protection against the post-cardiac arrest dysfunctions.